Overexpression of GATA2 predicts an adverse prognosis for patients with acute myeloid leukemia and it is associated with distinct molecular abnormalities

Vicente, Carmen; Vázquez, Iria; Conchillo, Ana; Garcı́a-Sánchez, Asunción; Marcotegui, Nerea; Fuster, Óscar; González, Marcos; Calasanz, Marı́a José; Lahortiga, Idoya; Odero, Marı́a D.

doi:10.1038/leu.2011.235

Cited by 70 publications

(59 citation statements)

References 11 publications

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“…The prognostic value of high GATA2 expression was most evident in adult CN-AML. 51,52 In the present study of pediatric AML, we did not observe a difference in survival based on GATA2 expression in CN-AML (n ϭ 40), which may be because of differences in distribution of genetic aberrations underlying pediatric compared with adult CN-AML. Interestingly, the prognostic impact of GATA2 was particularly high in specific morphologic and genetic AML subgroups.…”

Section: Gata2 As Prognostic Marker In Pediatric Aml 2071mentioning

confidence: 59%

“…High GATA2 expression identified a group of patients with a significant worse outcome among patients with high WT1 expression, which is consistent with recent observations in adult AML. 51 Moreover, in patients with FAB-M5 morphology and inv(16), we observed pronounced differences in survival between patients with high versus normal GATA2 expression, and a trend toward worse survival was observed in patients with 11q23 translocations or FLT3-ITD.…”

Section: Gata2 As Prognostic Marker In Pediatric Aml 2071mentioning

confidence: 79%

“…In adult AML, studies of the prognostic value of GATA2 have yielded conflicting results, which might be because of the relatively small patient cohorts and technical differences between studies in quantification of GATA2 expression. [49][50][51][52] In a cohort of 112 adult AML patients, Vicente et al showed recently that high GATA2 expression was associated with worse outcome (pOS, pEFS, and pDFS). The prognostic value of high GATA2 expression was most evident in adult CN-AML.…”

Section: Gata2 As Prognostic Marker In Pediatric Aml 2071mentioning

confidence: 99%

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High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia

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Hollink

Velden

et al. 2012

Blood

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In acute myeloid leukemia (AML), aberrant expression and mutations of transcription factors have been correlated with disease outcome. In the present study, we performed expression and mutation screening of GATA2, which is an essential transcription factor for regulation of myeloid lineage determination, in de novo pediatric AML patients. GATA2 mutations were detected in 5 of 230 patients, representing a frequency of 2.2% overall and 9.8% in cytogenetically normal AML. GATA2 expression analysis demonstrated that in 155 of 237 diagnostic samples (65%), GATA2 expression was higher than in normal BM. In complete remission, normalization of GATA2 expression was observed, whereas GATA2 expression levels stayed high in patients with resistant disease. High GATA2 expression at diagnosis was an independent poor prognostic factor for overall survival (hazard ratio [HR] ‫؍‬ 1.7, P ‫؍‬ .045), event-free survival (HR ‫؍‬ 2.1, P ‫؍‬ .002), and disease-free survival (HR ‫؍‬ 2.3, P ‫؍‬ .004). The prognostic impact of GATA2 was particularly evident in specific AML subgroups. In patients with French-American-British M5 morphology, inv(16), or high WT1 expression, significant differences in survival were observed between patients with high versus normal GATA2 expression. We conclude that high GATA2 expression is a novel poor prognostic marker in pediatric AML, which may contribute to better risk-group stratification and risk-adapted therapy in the future.

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Section: Gata2 As Prognostic Marker In Pediatric Aml 2071mentioning

confidence: 59%

Section: Gata2 As Prognostic Marker In Pediatric Aml 2071mentioning

confidence: 79%

Section: Gata2 As Prognostic Marker In Pediatric Aml 2071mentioning

confidence: 99%

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High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia

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Hollink

Velden

et al. 2012

Blood

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“…Overexpression of GATA2 frequently occurs in acute myelogenous leukemia (49,(75)(76)(77) and is associated with a poor prognosis (77). Gata2 overexpression is also found in tumors of nonhematopoietic origin, including neuroblastoma (78) and prostate cancer (79).…”

Section: Discussionmentioning

confidence: 99%

Histone Methyltransferase Setd8 Represses Gata2 Expression and Regulates Erythroid Maturation

Malik

Getman

Steiner

2015

Molecular and Cellular Biology

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Setd8 is the sole histone methyltransferase in mammals capable of monomethylating histone H4 lysine 20 (H4K20me1). Setd8 is expressed at significantly higher levels in erythroid cells than any other cell or tissue type, suggesting that Setd8 has an erythroidcell-specific function. To test this hypothesis, stable Setd8 knockdown was established in extensively self-renewing erythroblasts (ESREs), a well-characterized, nontransformed model of erythroid maturation. Knockdown of Setd8 resulted in impaired erythroid maturation characterized by a delay in hemoglobin accumulation, larger mean cell area, persistent ckit expression, incomplete nuclear condensation, and lower rates of enucleation. Setd8 knockdown did not alter ESRE proliferation or viability or result in accumulation of DNA damage. Global gene expression analyses following Setd8 knockdown demonstrated that in erythroid cells, Setd8 functions primarily as a repressor. Most notably, Gata2 expression was significantly higher in knockdown cells than in control cells and Gata2 knockdown rescued some of the maturation impairments associated with Setd8 disruption. Setd8 occupies critical regulatory elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1 and gain of H4 acetylation at the Gata2 1S promoter. These results suggest that Setd8 is an important regulator of erythroid maturation that works in part through repression of Gata2 expression.

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“…38 However, a function for Twist1 in either HSPC development or leukemogenesis has been largely unknown. In this study, high levels of Twist1 transcripts were observed in embryonic relative to adult HSPCs ( Figure 1B), suggesting that Twist1 functions in embryonic hematopoiesis.…”

mentioning

confidence: 99%

Twist1 regulates embryonic hematopoietic differentiation through binding to Myb and Gata2 promoter regions

et al. 2017

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Overexpression of GATA2 predicts an adverse prognosis for patients with acute myeloid leukemia and it is associated with distinct molecular abnormalities

Cited by 70 publications

References 11 publications

High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia

High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia

Histone Methyltransferase Setd8 Represses Gata2 Expression and Regulates Erythroid Maturation

Twist1 regulates embryonic hematopoietic differentiation through binding to Myb and Gata2 promoter regions

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